摘要
细胞色素P450(CYP)表达的性别依赖性可引起肝药物代谢的性别差异。生长激素是由垂体分泌的一种肽类激素,其分泌有性别差异,即雄性动物以脉冲式释放生长激素,而雌性动物的生长激素为持续性释放。性激素引起生长激素释放方式的不同是造成CYP性别依赖性表达的主要原因,根据受生长激素调控方式的不同可将CYP性别依赖性基因分为Ⅰ类和Ⅱ类基因。信号转导子和转录激活子5b和肝细胞核因子4α是参与生长激素对CYP表达调控的主要转录因子,可促进雄大鼠体内雄性依赖性CYP的表达而对雌性依赖性CYP表达产生抑制作用。生长激素可通过对CYP基因表观遗传的修饰引起其表达的性别特异性。本文将概述CYP性别依赖性表达的主要调控机制。
Gender differences in drug metabolism can be caused by sex-dependent expression of cytochrome P450 （CYP）. Growth hormone is a peptide hormone secreted by the pituitary. Plasma growth hormone profiles display sex differences, which are highly pulsatile （intermittent） in males but more frequent （nearly continuous） in females. The rea- son for sex-dependent expression of CYP is the pattern,of plasma growth hormone release regulated by sex-hormones. Sex-dependent genes can be classified into class I and class II genes based on their response to growth hormone. Signal transducer and activator of transcription5b and hepatic nuclear factor4a are key factors for the sex-dependent effects of growth hormone on the expression of CYP through their stimulatory effects on male-specific genes and inhibitory effects on female-specific genes. Growth hormone also causes sex-dependent expression of CYP by epigenetic regulation. This paper reviewed the main reoulatorv mechanisms of arowth hormone on sex-deDendent expression of CYP.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2013年第5期893-897,共5页
Chinese Journal of Pharmacology and Toxicology
基金
国家科技重大专项(2012ZX09301002-001-007)~~
